PB2484: IMMUNE PRIVILEGES OF NESTIN-GFP+ CELLS OF THE BONE MARROW ARE PRESERVED IN IMMUNOLOGICALLY COMPLETE IMMUNIZED WITH GFP MICE IN THE MODEL OF ECTOPIC FOCI OF HEMATOPOIESIS UNDER THE RENAL CAPSULE
Authors: Dmitriy Karpenko, Nikolay Kapranov, Aleksei Bogdanov, Alexander Lazutkin, Aleksei Bigildeev
Journal: HemaSphere (2023)

Topic: 23. Hematopoiesis, stem cells and microenvironment Background: Immune privileges (IPs) were demonstrated for stem cells of different tissue origins, such as hair follicle stem cells, muscle stem cells, and hematopoietic stem cells. Our recent results demonstrated that bone marrow mesenchymal stem cells (BM-MSCs) are immune privileged cells in the model of ectopic foci in mice (DOI: 10.3389/fcell.2022.993056). Aims: We continued our studies to answer how strong immune privileges of BM stem cells and their progeny are in the model of ectopic foci of hematopoiesis (EFHs) formation. Methods: We implanted bone marrow (BM) of F1 (Nestin-GFP x C57Bl/6) mice under the renal capsule of isogenic C57Bl/6 mice lacking transgene, which were beforehand immunized with GFP. The effectiveness of immunization for GFP was confirmed by ELISA. We considered three key aspects, which allowed us to demonstrate the phenomenon. The first one was that we concentrated our attention on a small compartment of stem cells rather then considering all mesenchymal cells to be immune privileged. The second one was that immunogenic marker was presented only on small subpopulation of transplanted cells, while the most cells were immunologically equivalent to the recipient. The third one was a usage of minimally disturbed BM fragments for transplantation. Results: The EFHs have been formed, and GFP-expressing cells were detected within the foci. The mean proportions of GFP+CD45+ and GFP+CD45– cells were 24.1*10-5 x÷ 3.8 and 0.8*10-5 x÷ 1.8, respectively. The corresponding values in non-immunised recipients were 2.3 × 10–5 ×÷10 and 2.0×10–5 ×÷9. Interestingly, there were no remarkable changes in the proportions of GFP+CD45– cells and there was an increase in the mean proportions of GFP+CD45+ cells as compared to non-immunized recipients, which implies differences in immune regulations for these populations. Our new results strengthen previous reports showing that GFP-expressing progenitors in EFH model can persist and contribute to the maintenance of hematopoietic territory for 6 weeks even in immunized recipients. That way we can speak that observed GFP+ progenitors are privileged against full and activated immune system of a recipient. Summary/Conclusion: We noted that such immune privileged stem cells may be also associated with nestin expression in adult mammals. This study contributes to a concept that full-fledged IPs are a property of quiescent stem cells in differend organs and tissues, a distinctive feature of which could be expression of nestin or activity of factors associated with nestin promoter. This comprehension provides a new perspective not only for understanding stem cells regulation in health, but for oncogenesis as well. Recognition of MSCs as immune privileged cells provides a new perspective for MSC-based therapies. Keywords: Mesenchymal stem cell, Mouse model, Bone marrow transplant, Immunity